GNF-2

製品コードS2899 バッチS289903

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈H₁₃F₃N₄O₂
	分子量	374.32	CAS No.	778270-11-4
Solubility (25°C)*	体外	DMSO	74 mg/mL (197.69 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl, shows no activity to Flt3-ITD, Tel-PDGFR, TPR-MET and Tel-JAK1 transformed tumor cells.
in vitro	GNF-2 causes a dose-dependent growth inhibition of the Bcr-abl–positive cell lines with IC50 values of 273 nM (K562) and 268 nM (SUP-B15). This compound inhibits the growth of Ba/F3.p210^E255V and Ba/F3.p185^Y253H cells with IC50 values of 268 nM and 194 nM respectively. This chemical (1 μM) induces apoptosis of Ba/F3.p210 cells as well as Ba/F3.p210^E255V cells. It inhibits the cellular tyrosine phosphorylation of Bcr-abl in a dose-dependent manner with IC50 of 267 nM. This compound (1 μM) induces a significant decrease in the levels of phospho-Stat5 in Ba/F3.p210 cells. It binds to the myristic binding pocket of Bcr-abl. ^[1] This inhibitor inhibits the kinase activity of non-myristoylated c-Abl more potently than that of myristoylated c-Abl by binding to the myristate-binding pocket in the C-lobe of the kinase domain. This agent (10 μM) requires BCR and/or the c-Abl SH3 and/or SH2 domains to inhibit BCR-Abl-dependent cell proliferation. It, but not a methylated GNF-2 analog, binds c-Abl in cellular extracts derived from 3T3 fibroblasts. This compound (10 μM), in a dose-dependent manner, clearly inhibits tyrosine phosphorylation of CrkII. It inhibits the phosphorylation of CrkII in c-AblG2A-expressing cells with IC50 of 0.051 μM. ^[2] This chemical binds in an extended conformation in the myristate pocket with the CF3-group buried at the same depth as the final two carbons of the myristate ligand. This compound (10 µM) combined with imatinib (1 µM) reduces the number of resistant clones to 1 µM imatinib by at least 90%. ^[3] It inhibits the auto-phosphorylation and proliferation of BafF3 cells expressing p210Bcr–Abl and p210Bcr–Abl mutants. This agent (8 nM) in combination with GNF-5 (20 nM) results in additive effects with respect to inhibition of the Abl64–515 kinase activity. ^[4]

製品説明

GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl, shows no activity to Flt3-ITD, Tel-PDGFR, TPR-MET and Tel-JAK1 transformed tumor cells.

in vitro

GNF-2 causes a dose-dependent growth inhibition of the Bcr-abl–positive cell lines with IC50 values of 273 nM (K562) and 268 nM (SUP-B15). This compound inhibits the growth of Ba/F3.p210^E255V and Ba/F3.p185^Y253H cells with IC50 values of 268 nM and 194 nM respectively. This chemical (1 μM) induces apoptosis of Ba/F3.p210 cells as well as Ba/F3.p210^E255V cells. It inhibits the cellular tyrosine phosphorylation of Bcr-abl in a dose-dependent manner with IC50 of 267 nM. This compound (1 μM) induces a significant decrease in the levels of phospho-Stat5 in Ba/F3.p210 cells. It binds to the myristic binding pocket of Bcr-abl. ^[1] This inhibitor inhibits the kinase activity of non-myristoylated c-Abl more potently than that of myristoylated c-Abl by binding to the myristate-binding pocket in the C-lobe of the kinase domain. This agent (10 μM) requires BCR and/or the c-Abl SH3 and/or SH2 domains to inhibit BCR-Abl-dependent cell proliferation. It, but not a methylated GNF-2 analog, binds c-Abl in cellular extracts derived from 3T3 fibroblasts. This compound (10 μM), in a dose-dependent manner, clearly inhibits tyrosine phosphorylation of CrkII. It inhibits the phosphorylation of CrkII in c-AblG2A-expressing cells with IC50 of 0.051 μM. ^[2] This chemical binds in an extended conformation in the myristate pocket with the CF3-group buried at the same depth as the final two carbons of the myristate ligand. This compound (10 µM) combined with imatinib (1 µM) reduces the number of resistant clones to 1 µM imatinib by at least 90%. ^[3] It inhibits the auto-phosphorylation and proliferation of BafF3 cells expressing p210Bcr–Abl and p210Bcr–Abl mutants. This agent (8 nM) in combination with GNF-5 (20 nM) results in additive effects with respect to inhibition of the Abl64–515 kinase activity. ^[4]

プロトコル(参考用のみ)

キナーゼアッセイ	Binding assay
キナーゼアッセイ	Recombinant proteins (100 nM for each construct) or immunoprecipitated proteins are diluted in kinase buffer (20 mM HEPES (pH 7.4), 50 mM KCl, 0.1% CHAPS, 30 mM MgCl₂, 2 mM MnCl₂, 1 mM DTT, and 1% glycerol). Aliquots of the diluted proteins are preincubated with either DMSO or this compound for 30 min at room temperature and then added to K-LISA PTK EAY reaction plates. The kinase reaction is initiated by adding 0.1 mM ATP and is allowed to proceed for 30 min at room temperature. The phosphorylation of GST-Abltide is monitored by SDS-PAGE and phosphorimaging analysis or autoradiography.
細胞アッセイ	細胞株	Ba/F3.p210, Ba/F3.p210^E255V and Ba/F3.p185^Y253H cells
	濃度	~10 μM
	反応時間	48 hours
	実験の流れ	Cells (0.3-0.6 × 10⁶ per mL) are plated in duplicate or triplicate in 96-well plates containing increasing GNF-2 concentrations (5 nM–10 μM). After incubation at 37 ℃ in 5% CO₂ for 48 hours, the effect of this compound on cell viability is determined by the MTT colorimetric dye reduction method. Inhibition of cell proliferation is calculated as a percentage of growth of DMSO-treated cells, and IC50 values are determined with Microsoft Excel XLfit3.

参考

https://pubmed.ncbi.nlm.nih.gov/16415863/
https://pubmed.ncbi.nlm.nih.gov/19679652/
https://pubmed.ncbi.nlm.nih.gov/20072125/

https://pubmed.ncbi.nlm.nih.gov/20152788/

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カスタマーフィードバック

: Data from [Data independently produced by , , Oncotarget, 2017, 8(24):38717-38730]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

A multiplexed siRNA screen identifies key kinase signaling networks of brain glia [ Life Sci Alliance, 2023, 6(5)e202201605]	PubMed: 36878638
Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK [ Clin Sci (Lond), 2021, 135(19):2243-2263]	PubMed: 34569605
Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement [Vasta JD Cell Chem Biol, 2018, 25(2):206-214]	PubMed: 29174542
Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis [ Sci Signal, 2018, 11(518)eaao0422]	PubMed: 29463776
Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis [ Sci Signal, 2018, 11(518)eaao0422]	PubMed: 29463776
Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. [ J Gen Virol, 2018, 99(5):619-630]	PubMed: 29557770
Comparative Characterization of Osteoclasts Derived From Murine Bone Marrow Macrophages and RAW 264.7 Cells Using Quantitative Proteomics. [ JBMR Plus, 2018, 2(6):328-340]	PubMed: 30460336
Abl kinase regulation by BRAF/ERK and cooperation with Akt in melanoma. [ Oncogene, 2017, 36(32):4585-4596]	PubMed: 28368422
Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells. [Tsubaki M, et al. Oncotarget, 2017, 8(24):38717-38730]	PubMed: 28418880

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人間や獣医の診断であるか治療的な使用のためにでない。

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